PB2109: PROGNOSTIC VALUE OF MYC STRUCTURAL VARIATIONS IDENTIFIED BY FISH IN TRANSPLANT ELIGIBLE MULTIPLE MYELOMA PATIENTS
Authors: Ines Dos Santos Marques, Maria José Soares, Aida Barbosa, Ian Calderon, Marta Henriques, Cátia Sol Reis, Pedro Baptista, André Pardal, Jorge Cancela Pires, Eliana Aguiar, Rui Bergantim, Fernanda Trigo
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Primary genetic abnormalities, characterized by recurrent immunoglobulin heavy chain structural variations (SV) and/or hyperdiploidy occur at an early stage of the disease, while secondary genetic abnormalities such as 1q gain, 17p deletion and SV involving the Primary genetic abnormalities, characterized by recurrent immunoglobulin heavy chain structural variations (SV) and/or hyperdiploidy occur at an early stage of the disease, while secondary genetic abnormalities such as 1q gain, 17p deletion and SV involving the Primary genetic abnormalities, characterized by recurrent immunoglobulin heavy chain structural variations (SV) and/or hyperdiploidy occur at an early stage of the disease, while secondary genetic abnormalities such as 1q gain, 17p deletion and SV involving the MYCMYCMYC proto-oncogene arise upon Multiple myeloma (MM) progression. These genetic alterations contribute to disease heterogeneity and impact the response to therapy and prognosis. proto-oncogene arise upon Multiple myeloma (MM) progression. These genetic alterations contribute to disease heterogeneity and impact the response to therapy and prognosis. proto-oncogene arise upon Multiple myeloma (MM) progression. These genetic alterations contribute to disease heterogeneity and impact the response to therapy and prognosis. Aims: The aim of this study was to analyze the impact of SV involving the The aim of this study was to analyze the impact of SV involving the The aim of this study was to analyze the impact of SV involving the MYCMYCMYC gene in patients with MM. gene in patients with MM. gene in patients with MM. Methods: This retrospective study evaluated MM patients aged ≥18 years, eligible for autologous hematopoietic cell transplantation (AHCT), who were followed up in a tertiary hospital between January 2007 and December 2020. Fluorescence in situ hybridization (FISH) using break apart probes for the This retrospective study evaluated MM patients aged ≥18 years, eligible for autologous hematopoietic cell transplantation (AHCT), who were followed up in a tertiary hospital between January 2007 and December 2020. Fluorescence in situ hybridization (FISH) using break apart probes for the This retrospective study evaluated MM patients aged ≥18 years, eligible for autologous hematopoietic cell transplantation (AHCT), who were followed up in a tertiary hospital between January 2007 and December 2020. Fluorescence in situ hybridization (FISH) using break apart probes for the MYCMYCMYC gene was used to evaluate the patients. gene was used to evaluate the patients. gene was used to evaluate the patients. Clinical and demographic data were analysed using the IBM SPSS Statistics 26® program.Clinical and demographic data were analysed using the IBM SPSS Statistics 26® program.Clinical and demographic data were analysed using the IBM SPSS Statistics 26® program. Results: A total of A total of A total of 124 patients [54,8% male (n=68), 45,2% female (n=56)] were included, with a median age at diagnosis of 59 years (37-69). The most frequent MM subtype was IgG/kappa (35.5%, n=44). At diagnosis, the most common ‘CRAB’ symptoms were bone disease (63,7%, n=79) and anemia (52,4%, n=65) followed by kidney failure (21,0%, n=26) and hypercalcemia (20,2%, n=25). The revised MM International Staging System (R-ISS) was applied in 72,6% (n=90) patients [stage I: 13,3% (n=12); stage II: 60,0% (n=54), and stage III: 26,7% (n=24)]. FISH analysis at diagnosis revealed absence of rearrangement in 83,9% (n=104), presence of rearrangement in 10,5% (n=13), increased copy number in 3,2% (n=4) and deletion of the 124 patients [54,8% male (n=68), 45,2% female (n=56)] were included, with a median age at diagnosis of 59 years (37-69). The most frequent MM subtype was IgG/kappa (35.5%, n=44). At diagnosis, the most common ‘CRAB’ symptoms were bone disease (63,7%, n=79) and anemia (52,4%, n=65) followed by kidney failure (21,0%, n=26) and hypercalcemia (20,2%, n=25). The revised MM International Staging System (R-ISS) was applied in 72,6% (n=90) patients [stage I: 13,3% (n=12); stage II: 60,0% (n=54), and stage III: 26,7% (n=24)]. FISH analysis at diagnosis revealed absence of rearrangement in 83,9% (n=104), presence of rearrangement in 10,5% (n=13), increased copy number in 3,2% (n=4) and deletion of the 124 patients [54,8% male (n=68), 45,2% female (n=56)] were included, with a median age at diagnosis of 59 years (37-69). The most frequent MM subtype was IgG/kappa (35.5%, n=44). At diagnosis, the most common ‘CRAB’ symptoms were bone disease (63,7%, n=79) and anemia (52,4%, n=65) followed by kidney failure (21,0%, n=26) and hypercalcemia (20,2%, n=25). The revised MM International Staging System (R-ISS) was applied in 72,6% (n=90) patients [stage I: 13,3% (n=12); stage II: 60,0% (n=54), and stage III: 26,7% (n=24)]. FISH analysis at diagnosis revealed absence of rearrangement in 83,9% (n=104), presence of rearrangement in 10,5% (n=13), increased copy number in 3,2% (n=4) and deletion of the MYC MYC MYC gene in 2,4% (n=3). Multivariate logistic regression analysis found no association between SV involving the gene in 2,4% (n=3). Multivariate logistic regression analysis found no association between SV involving the gene in 2,4% (n=3). Multivariate logistic regression analysis found no association between SV involving the MYCMYCMYC gene and the presence of anemia, bone disease, hypercalcemia or kidney failure (gene and the presence of anemia, bone disease, hypercalcemia or kidney failure (gene and the presence of anemia, bone disease, hypercalcemia or kidney failure (ppp=0.227). Additionally, no association was found with other cytogenetic alterations, namely t(4;14), t(11;14), t(14;16), 1q gain, 13p or 17p deletion (=0.227). Additionally, no association was found with other cytogenetic alterations, namely t(4;14), t(11;14), t(14;16), 1q gain, 13p or 17p deletion (=0.227). Additionally, no association was found with other cytogenetic alterations, namely t(4;14), t(11;14), t(14;16), 1q gain, 13p or 17p deletion (ppp=0.906). Moreover, no association was found between SV involving the =0.906). Moreover, no association was found between SV involving the =0.906). Moreover, no association was found between SV involving the MYCMYCMYC gene and the response to induction therapy (gene and the response to induction therapy (gene and the response to induction therapy (ppp=0.657). Relapse after AHCT was more frequent in patients who had SV involving the =0.657). Relapse after AHCT was more frequent in patients who had SV involving the =0.657). Relapse after AHCT was more frequent in patients who had SV involving the MYCMYCMYC gene compared to patients without alterations in the gene compared to patients without alterations in the gene compared to patients without alterations in the MYCMYCMYC gene [gene [gene [ppp=0.019, 95% confidence interval (CI) 1,284-16,873)]. The estimated time to progression was 23 months in patients with SV involving the =0.019, 95% confidence interval (CI) 1,284-16,873)]. The estimated time to progression was 23 months in patients with SV involving the =0.019, 95% confidence interval (CI) 1,284-16,873)]. The estimated time to progression was 23 months in patients with SV involving the MYCMYCMYC gene (95% CI 7,661-38,339) and 43 months in patients without the presence of these alterations (95% CI 35,603-50,397) (gene (95% CI 7,661-38,339) and 43 months in patients without the presence of these alterations (95% CI 35,603-50,397) (gene (95% CI 7,661-38,339) and 43 months in patients without the presence of these alterations (95% CI 35,603-50,397) (ppp=0.001). Although patients who underwent maintenance therapy after AHCT showed, overall, a longer time to disease progression [69 months (95% CI 32,031-105,969) =0.001). Although patients who underwent maintenance therapy after AHCT showed, overall, a longer time to disease progression [69 months (95% CI 32,031-105,969) =0.001). Although patients who underwent maintenance therapy after AHCT showed, overall, a longer time to disease progression [69 months (95% CI 32,031-105,969) versusversusversus 33 months (95% CI 28,526-37,474)], patients with SV involving the 33 months (95% CI 28,526-37,474)], patients with SV involving the 33 months (95% CI 28,526-37,474)], patients with SV involving the MYCMYCMYC gene present earlier disease progression than patients without with SV involving the gene present earlier disease progression than patients without with SV involving the gene present earlier disease progression than patients without with SV involving the MYCMYCMYC gene [39 months (CI 95% 20,539-57,461) gene [39 months (CI 95% 20,539-57,461) gene [39 months (CI 95% 20,539-57,461) versusversusversus 69 months (IC 95% 28.557-109.443), 69 months (IC 95% 28.557-109.443), 69 months (IC 95% 28.557-109.443), ppp=0.002].=0.002].=0.002]. Summary/Conclusion: Although SV involving the Although SV involving the Although SV involving the MYCMYCMYC gene, at diagnosis, have already been associated with “CRAB” symptoms, high-risk cytogenetic alterations and response to induction therapy in MM, in this population these associations were not verified. However, the presence of SV involving the gene, at diagnosis, have already been associated with “CRAB” symptoms, high-risk cytogenetic alterations and response to induction therapy in MM, in this population these associations were not verified. However, the presence of SV involving the gene, at diagnosis, have already been associated with “CRAB” symptoms, high-risk cytogenetic alterations and response to induction therapy in MM, in this population these associations were not verified. However, the presence of SV involving the MYCMYCMYC gene seems to contribute to an early relapse of MM, despite maintenance with lenalidomide after AHCT, suggesting that these patients will have a more aggressive MM behavior. The study highlights the importance of evaluating gene seems to contribute to an early relapse of MM, despite maintenance with lenalidomide after AHCT, suggesting that these patients will have a more aggressive MM behavior. The study highlights the importance of evaluating gene seems to contribute to an early relapse of MM, despite maintenance with lenalidomide after AHCT, suggesting that these patients will have a more aggressive MM behavior. The study highlights the importance of evaluating MYCMYCMYC gene rearrangement by FISH at diagnosis as it may have a high prognostic value and impact treatment decisions for MM patients. gene rearrangement by FISH at diagnosis as it may have a high prognostic value and impact treatment decisions for MM patients. gene rearrangement by FISH at diagnosis as it may have a high prognostic value and impact treatment decisions for MM patients. Keywords: Autologous hematopoietic stem cell transplantation, Multiple myeloma, Prognosis, MYC